Melissa Maginnis, Ph.D.
B.S. (2001) Neumann College
Ph.D. (2007) Vanderbilt University
Postdoctoral Training: Brown University
Research in the Maginnis laboratory is focused on understanding the cellular and molecular basis of viral disease. Specifically, our work seeks to define the viral and host cell factors that regulate infection and viral pathogenesis of the human JC polyomavirus (JCPyV). The majority of the population is infected with JCPyV, which establishes a lifelong, persistent infection in the kidney without symptoms. In immunocompromised hosts, such as individuals receiving immunomodulatory therapies for autoimmune diseases or those with HIV, the virus can spread from the kidney to the central nervous system and cause a lytic infection in the brain. Viral destruction of the glial cells astrocytes and oligodendrocytes, which are critical for myelin production, results in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There is currently no effective treatment for PML.
Viruses are complex, yet extremely efficient machines that hijack the host cell machinery to complete an infectious cycle and produce progeny virus. The interplay between JCPyV and host cell factors is critical to understanding disease outcomes and PML pathogenesis. Research in my laboratory is focused on understanding the detailed molecular interactions between the virus and host cell factors that drive the early steps in the infectious cycle including entry, trafficking, and viral transcription. In particular, we are focused on defining how JCPyV uses the serotonin receptor to transverse the plasma membrane, identifying signaling cascades that drive viral transcription, and elucidating how the virus causes persistent and lytic infections. This research will allow us to define key unanswered questions in JCPyV biology, provide crucial insights into JCPyV pathogenesis, and identify novel targets for rational drug design for prevention and treatment of PML.
- Mayberry, C.L., Nelson, C.D.S., and Maginnis, M.S. JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics. Current Clinical Microbiology Reports. In press.
Dimitriadi, M., Derdowski, A., Kalloo, G., Maginnis, M.S., O’Hern, P., Bliska, B., Sorkaç, A., Nguyen, K.C., Cook, S.J., Poulogiannis, G., Atwood, W.J., Hall, D.H., and Hart, A.C. (2016). Decreased function of survival motor neuron protein impairs endocytic pathways. Proc Natl Acad Sci USA;113(30):E4377-86.
- Ströh, L.J.*, Maginnis, M.S.*,+, Blaum, B.S., Nelson, C.D.S., Neu, U., Gee, G.V., O’Hara, B.A., Motamedi, N., DiMaio, D., Atwood, W.J., and Stehle, T. (2015). Increased affinity of JC Polyomavirus capsid for LSTc over other sialylated glycans is a major determinant of infectivity. Journal of Virology, 89(12):6364-75. *, Denotes equal contribution.
- Maginnis, M.S., Nelson, C.D.S., and Atwood, W.J. (2014). JC Polyomavirus Attachment, Entry, and Trafficking: Unlocking the Keys to a Fatal Infection. Journal of Neurovirology. In press.
- Bouley, S.J., Maginnis, M.S., Derdowski, A., Gee, G.V., O’Hara, B.A., Nelson, C.D., Bar, A.M, Atwood W.J., and Dugan, A.S. (2014). Host Cell Autophagy Promotes BK Virus Infection.Virology, 456–457:87–95.
- Zins, S.R., Nelson, C.D., Maginnis, M.S., Banerjee, R., O’Hara, B.A., and Atwood, W.J. (2013).The Human Alpha Defensin HD5 Neutralizes JC Polyomavirus Infection by Reducing ER Traffic and Stabilizing the Viral Capsid. Journal of Virology, 88(2):948-60.
- Assetta, B., Maginnis, M.S., Gracia Ahufinger, I., Haley, S.A., Gee, G.V., Nelson, C.D., O’Hara, B.A., Allen-Ramdial, S.A., and Atwood, W.J. (2013). 5-HT2 Receptors Facilitate JC Polyomavirus Entry. Journal of Virology, 87(24):13490-8.
- Maginnis, M.S., Ströh, L.J., Gee, G.V., O’Hara, B.A., Derdowski, A., Stehle, T., and Atwood, W.J. (2013). PML-associated Mutations in the JC Polyomavirus Capsid Disrupt LSTc Binding. mBio, 4(3) e00247-13.
- Nelson, C.D., Derdowski, A., Maginnis, M.S., O’Hara, B., and Atwood, W.J. (2012). The VP1 Subunit of JC Polyomavirus Recapitulates Early Events in Viral Trafficking and is a Novel Tool to Study Polyomavirus Entry. Virology, 428(1):30-40.
- Neu, U.*, Maginnis, M.S.*, Palma, A.S., Ströh, L.J., Nelson, C.D., Feizi, T., Atwood, W.J., and Stehle, T. (2010). Structure-Function Analysis of the Human JC Polyomavirus Establishes the LSTc Pentasaccharide as a Functional Receptor Motif. Cell Host & Microbe, 8(4):309-19.[Feature Article, Cover Illustration]. *, Denotes equal contribution.
- Maginnis, M.S., Haley S.A., Gee, G.V., and Atwood, W.J. (2010). Role of N-linked Glycosylation of the 5-HT2A Receptor in JC Virus Infection. Journal of Virology, 84(19):9677-84.
- Gasparovic, M.L., Maginnis, M.S., O’Hara, B.A., Dugan, A.S., and Atwood, W.J. (2009).Modulation of PML Protein Expression Regulates JCV Infection. Virology, 390(2):279-88.
- Maginnis, M.S. and Atwood, W.J. (2009). JC Virus: An Oncogenic Virus in Animals andHumans? Seminars in Cancer Biology, 19(4):261-9.
- Cseke, G. *, Maginnis, M.S.*, Cox, R.G. *, Tollefson, S.J., Podsiad, A.B., Wright, D.W., Dermody, T.S., and Williams, J.W. (2009). Integrin avb1 Promotes Infection by Human Metapneumovirus.PNAS, 106(5):1566-71. *, Denotes equal contribution.
- Dugan, A.S., Maginnis, M.S., Jordan, J.A., Gasparovic, M.L., Manley, K., Page, R., Williams, G., Porter, E., O’Hara, B.A., and Atwood, W.J. (2008). Human a-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells. The Journal of Biological Chemistry, 283(45):31125-32.
- Maginnis, M.S., Mainou, B.A., Derdowski, A., Johnson, E.M., Zent, R., and Dermody, T.S. (2008).NPXY Motifs in the b1 Integrin Cytoplasmic Domain Are Required for Functional Reovirus Entry. Journal of Virology, 82:3181-3191.
- Kobayashi, T., Antar, A.A.R., Boehme, K.W., Danthi, P., Eby, E.A., Guglielmi, K.M., Holm, G.H., Johnson, E.M., Maginnis, M.S., Naik, S., Skelton, W.B., Wetzel, J.D., Wilson, G.J., Chappell, J.D., and Dermody, T.S. (2007). A Plasmid-Based Reverse Genetics for Animal Double-Stranded RNA Viruses. Cell Host & Microbe, 1:147-157.
- Maginnis, M.S., Forrest, J.C., Dickeson, S.K., Santoro, S.A., Zutter, M.M., Nemerow, G.R., Bergelson, J.M., and Dermody, T.S. (2006). b1 Integrin Mediates Internalization of Mammalian Reovirus. Journal of Virology, 80:2760-2770. [Cover Illustration].